Scientists unlock cause of a mysterious vascular disease that affects one in 20 women

Scientists have discovered one of the major drivers of fibromuscular dysplasia, a condition which affects the body's arteries.

New research from an international team of scientists has shed light on a major driver of fibromuscular dysplasia or FMD, which can cause stroke, heart attack, kidney failure, and aneurysm.

It’s a significant step forward in understanding this disease, which affects the walls in the body’s arteries and is thought to affect up to 5% of women. It could also lead to new treatments for FMD.

Dr Jason Kovacic, CEO of the Victor Chang Cardiac Research Institute and Professor of Cardiovascular Research at UNSW Sydney, initiated the study more than 10 years ago while at the Icahn School of Medicine at Mount Sinai in New York, where he still maintains a laboratory today.

The researchers recruited 154 women for the study - half of whom had FMD and half who were otherwise healthy. They pinpointed the genetic differences and discovered that a major gene called UBR4 plays a crucial role in driving FMD by affecting the structure of the body’s arteries.

This breakthrough published in Nature Cardiovascular Research is even more exciting because it opens up first-of-its-kind therapeutic targets for this newly found biological pathway.

Prof. Kovacic says: “We know that changes in collagen and the structure of the body’s arteries are at the core of this disease, and one of the major drivers of this disease is UBR4, which controls an entire network of genes associated with FMD.  

“Ten years ago, we knew next to nothing about what causes FMD; now we not only know a major driver of this disease, but we also have several exciting therapeutic targets.”

One in 20 women is thought to have FMD, but most have no symptoms. The average age for diagnosis is around 50-55 years old, and 90-95% of people with FMD are women.

FMD affects the body’s arteries, most commonly the renal arteries and those that go to the brain (the carotid and vertebral arteries). It can either weaken or harden them, leading to aneurysm, dissection (like a tearing of an artery), or narrowing. Unlike other vascular diseases, such as atherosclerosis, it’s not driven by a build-up of plaque.

To uncover the cause of FMD, the researchers used skin biopsies to grow fibroblast cells to identify differences between the patients with FMD and the control group.

By creating the first-ever mouse models of FMD, they then succeeded in recreating one of FMD’s key features in humans: when vessels dilate and increase in size, they can cause aneurysms. They showed that changes in collagen and matrix proteins were affecting the artery wall, and the UBR4 gene was driving this change.

Prof. Kovacic, who is also a cardiologist at St Vincent’s Hospital in Sydney, adds that whilst this breakthrough may one day lead to the first-ever treatment for FMD, there still needs to be far greater awareness about the disease.

“Most people have never heard of FMD, and there will be people in the community, primarily women, who will be suffering from this disease and possibly being misdiagnosed.

“This can be a devastating disease, but if caught early, it can be managed. Hopefully, in the future, we will also be able to treat it far more successfully.”